title: Hyperdiploidy with 49-65 chromosomes represents a heterogeneous cytogenetic subgroup of acute myeloid leukemia with differential outcome.
abstract: Chromosome gain is frequent in acute myeloid leukemia (AML) and is counted alongside structural abnormalities when determining karyotype complexity. However, there are few studies investigating the cytogenetic profile and outcome of patients with a hyperdiploid karyotype (49-65 chromosomes, HK). We identified 221 (14%) patients with HK out of 1563 patients with three or more chromosomal abnormalities. HK was not associated with sex, white cell count and secondary disease status, but was more prevalent among children (22% vs 13%). The pattern of chromosomal gain and loss was non-random and chromosomes 8, 13 and 21 were the most frequently gained. Three distinct subgroups (numerical, structural and adverse) were identified with differential outcome: 5-year cumulative incidence of relapse of 52%, 68% and 76%, respectively (P=0.008). Patients in the adverse subgroup had poorer survival compared with patients with only numerical abnormalities (adjusted hazard ratio: 2.01 (95% confidence interval: 1.43-2.83), P=0.0002). This outcome heterogeneity was similar among children and adults. In conclusion, AML patients with a HK should not automatically be assigned to the adverse cytogenetic risk group on the basis of complexity. Instead they should be assessed for the presence of specific chromosomal abnormalities, which are known to harbour an adverse effect.
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Level 5, Sir James Spence Institute, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: L
authors.initials: L
authors.lastname: Chilton
authors.affiliation: Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: R K
authors.initials: RK
authors.lastname: Hills
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Level 5, Sir James Spence Institute, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Harrison
authors.affiliation: Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Burnett
authors.affiliation: Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Grimwade
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Level 5, Sir James Spence Institute, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: A V
authors.initials: AV
authors.lastname: Moorman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011123:Polyploidy; D011379:Prognosis; D055815:Young Adult